- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
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- by Martinez-Flores, R., Super, H., Sanchez-Martinez, J., Solis-Urra, P., Ibanez, R., Herold, F., Paas, F., Mavilidi, M., Zou, L., Cristi-Montero, C.Background: Physical activity has been associated with better reading comprehension and reduces cognitive load (CL), but the role of brain volume in modulating this relationship remains unclear. Therefore, this study aims to determine whether the gray matter volume in key regions modulates the effects of different physical activity modalities on reading comprehension and associated CL. Methods: Thirteen male adolescents (12-13 years). Adolescents with MRI data participated in a randomized cross-over trial comparing three conditions: 1) sedentary behavior (SC, emulating a […]
- by Matsche, J., Fauser, J., Bansal, T., Leschinsky, N., Coleman, C., Karginov, A. V.Optogenetics enables researchers to control protein localization, interactions, and activity using photosensitive domains. The key desired properties for optogenetic tools include broad applicability, tight light-regulated control with high dynamic range, and tunability. Previously, we described an engineered light-sensitive switch, LightR, composed of two VVD domains connected by a flexible linker, enabling light-dependent allosteric control of protein activity through site-specific insertion. Here, we introduce enhanced LightR variants with improved dynamic range and faster activation kinetics. Through targeted modifications to the VVD […]
- by Zhou, B. P., Chu, T. L. H., Gallant, A. K., Wang, S., Bhat, T. A., Ghorayeb, R., Gough, C., Garcia, R. E., Pujana, M. A., Lim, C. J., Maxwell, C. A.The metastatic process initiates with collective cell invasion into surrounding tissues and axillary nodes, and subsequent colonization at a distant site. Previously, we found collective invasion is augmented during the G2 cell cycle phase, facilitated through Aurora kinase A (AURKA)-mediated centrosome polarization in the leader cell. Here, we identify cell cycle-associated gene signatures as overrepresented in axilla and liver metastatic sites, with AURKA expression strongly correlated with breast cancer metastasis signatures, and pan-cancer patient survival. Then, we show GFP-AURKA expression […]
- by Milkey, A., Chen, J., Lewis, P. O.As modern phylogenomics datasets become increasingly large, it is useful to develop recommendations for how to subsample datasets for best species tree inference. Here we apply a new measure of phylogenetic information content that estimates the reduction in tree space occupied by a posterior sample of inferred trees relative to a prior sample in order to assess the effects of gene tree parameters on species tree estimation. We find that, consistent with earlier studies, when data are informative, more data […]
- by Joerg, M., Walz, L., Lander, M., bessler, l., Nathal, s., Freude, K. K., Endres, K., Helm, M., Friedland, K.tRNA modifications are critical regulators of RNA stability, decoding fidelity, and cellular stress adaptation, yet their contribution to human neurodegenerative disease remains poorly understood. Beyond their established functions in translational control, emerging evidence shows that RNA modifications influence neurogenesis, neurodevelopment, neuronal function, brain-cell differentiation, and cellular plasticity. Consequently, dysregulation of these molecular processes is increasingly recognized as a mechanistic contributor to neurodegenerative disorders. Alzheimers disease (AD), characterized by amyloid pathology, synaptic dysfunction, and progressive neuronal loss, has recently been linked […]
- by Mabry, K. N., Donahue, E. K. F., Orgel, A. D., Keuchel, B., Kushner, M. G., Burkewitz, K.The neuronal endoplasmic reticulum (ER) extends from the soma into axons and dendrites to coordinate protein trafficking, lipid metabolism, inter-organelle organization, and calcium homeostasis. Conserved genes involved in shaping the tubular ER are implicated in neurodevelopment and neurodegeneration, suggesting that ER structure and dynamics influence neuronal health and drive pathogenesis. However, the links between ER morphology and neuronal function and resilience remain incompletely understood. While models typically depict the neuronal ER as a fully continuous network, here we show that […]
- by Gouirand, N., Ibrahimi, M., Valotteau, C., Lecouffe, B., Le Bivic, A., Massey Harroche, D., Rico, F., Merkel, M., Delacour, D., Bazellieres, E.The development, maintenance and repair of epithelial tissues critically rely on adhesion complexes that ensure structural integrity while enabling dynamic remodeling. Such tissue remodeling underpins both physiological morphogenesis and pathological transformation. Central to these processes are mechanical forces, which tightly couple cytoskeletal organization to adhesion dynamics. Despite extensive investigations in two dimensional (2D) systems, how these interactions are orchestrated within polarized three dimensional (3D) epithelia remains largely unresolved. Here, we introduce a new, non invasive strategy to probe localized force […]
- by Okino, M.-L., Zhu, H., Corban, S., Benaglio, P., Djulamsah, J., OMahony, B., Vanderstel, K., Elgamal, R., Miller, M., Wang, A., Sander, M., Gaulton, K. J.Endoplasmic reticulum (ER) stress in pancreatic beta cells contributes to impaired function and type 2 diabetes (T2D). In this study we performed genome-wide perturbation screens and genomic profiling in beta cells to identify novel mediators of ER stress responses and diabetes risk. We defined gene regulatory networks in beta cells and identified specific beta cell networks enriched for T2D risk variants with altered expression in ER stress. We performed a loss-of-function CRISPR screen for survival under ER stress in EndoC-{beta}H1 […]
- by Gillies, G. J., Dungey, M. P., Eckert, C. G.1. Changes in habitat structure across species distributions may contribute to the generation and maintenance of range limits, but few studies have evaluated this by directly measuring habitat availability across relevant spatial scales. 2. Here, we test the predictions that coarse-scale and patch-level habitat availability decline towards and beyond the northern range limit of Pacific coastal dune endemic Camissoniopsis cheiranthifolia. We used aerial imagery and geographic information system (GIS) tools to measure the coarse-scale availability of coastal dune habitat in […]
- by Ing-Jeng, C., Latreche, A., A. Ross, S., Almonacid, J., JM Dick, T., Vereecke, E., Wakeling, J.Muscle mass significantly influences skeletal muscle behaviour, potentially explaining why traditional massless Hill-type models struggle to predict the forces generated by larger muscles during dynamic, submaximal contractions. However, the applicability of mass-enhanced Hill-type models in human locomotion remains unexplored. Here, we compared the predicted force from a 1D mass-enhanced Hill-type muscle model with a traditional 1D massless Hill-type muscle model across a range of experimentally measured human movements. Kinematic and electromyographic data were collected from twenty participants performing locomotor tasks […]
- by Li, S., Chauvin, P., Gross, O., Bailey, M., Jager, S.We introduce mRNA-GPT, a generative model for end-to-end full-length mRNA sequence design and optimization. Unlike existing approaches that optimize isolated regions, mRNA-GPT jointly optimizes across all three regions (5' UTR, CDS, and 3' UTR) to capture long-range sequence dependencies and cross-region regulatory interactions critical for therapeutic efficacy. The model is pre-trained on 30 million full-length natural mRNA sequences across diverse species and organisms, establishing a robust foundation for sequence generation. We employ Reinforcement Learning (RL), specifically Proximal Policy Optimization (PPO) […]
- by Ihejirika, P., Rai, D., Rosenberg, M., Xu, J.Stroke impairs dexterous hand use in daily activities, which may be due to compromised coordination complexity and diminished task-appropriate and individually-distinctive coordination (expressiveness). This loss of complexity and expressiveness, however, has not been elucidated, especially in spatiotemporal coordination. Here, we characterized spatiotemporal coordination in able-bodied and post-stroke hands during finger individuation. We quantified coordination complexity and expressiveness using principal component analysis (PCA) and linear discriminant analysis of 3D isometric forces from all five fingers. Paretic fingers showed reduced complexity (number […]
- by Floriou-Servou, A., Weber, R., Chen, Y., Kooiker, C. L., Tetzlaff, M. R., Birnie, M. T., Short, A. K., Roberts, R., Liang, H. Y., Gantuz, M., Hardy, M., Mortazavi, A., Baram, T. Z.Early-life adversity (ELA) is strongly linked to emotional disorders characterized by dysregulated reward behaviors including diminished motivation for and enjoyment of rewards (anhedonia). However, how transient ELA leads to enduring disruptions of reward behaviors remains unclear. Using activity-dependent genetic labeling during ELA, we previously found that the paraventricular thalamic nucleus (PVT) uniquely distinguishes ELA from typical rearing, and inhibiting ELA-activated PVT cells in adult ELA mice rescued reward behaviors in a sex-specific manner. However, the cellular mechanisms by which ELA […]
- by Wojcik, M., Orłowski, P., Adamczyk, S., Lenartowicz, P., Hobot, J., Wierzchon, M., Bola, M.Background: Contemporary research indicates that psychedelics induce notable neurophysiological changes, some lasting weeks to months after a single dose. However, most evidence derives from acute administration studies and limited post-acute follow-ups. Long-term naturalistic psychedelic users remain critically underexamined, yet may exhibit distinct neurobiological profiles informing our understanding of persistent alterations following repeated exposure. Methods: We recorded resting-state EEG in 57 long-term psychedelic users (abstinent [≥]30 days) and 49 matched non-users across two independent sites under eyes-open and eyes-closed conditions. We […]
- by Juarez-Contreras, I., Kim, H., Budin, I.A hallmark of eukaryotic membranes is the pairing of lineage-specific sterols with characteristic sphingolipid species. Mammalian cell membranes are enriched in both cholesterol and long-chain sphingolipids like sphingomyelin, whereas fungi synthesize ergosterol and very long-chain sphingolipids with sugar-containing head groups. It has been proposed that these two lipid classes co-evolved to support membrane structure and organization. Here we investigated how sterol structure and sphingolipid chain length together control membrane order and phase behavior. In the yeast Saccharomyces cerevisiae, loss of […]
- by Montague, T. G., Rubino, F. A., Gibbons, C. J., Mungioli, T. J., Small, S. T., Coffing, G. C., Kern, A. D.The coleoid cephalopods (octopus, cuttlefish, and squid) are emerging model organisms for neuroscience, development, and evolutionary biology. Determining their sex early in life is critical for population management and controlled experiments. Here, we present a protocol to non-invasively determine the sex of multiple cephalopod species as young as 3 hours post-hatching using a skin swab and quantitative PCR (qPCR). We describe steps for designing qPCR primers, swabbing live animals, extracting DNA, running the qPCR, and analyzing the results. For complete […]
- by Domingues-Silva, B., Azzalin, C. M.Mammalian telomeric DNA comprises long tracts of tandem TTAGGG repeats. The same repeats are also found at internal chromosomal regions called interstitial telomeric sequences (ITSs). Telomeres are transcribed into UUAGGG-containing transcripts, named TERRA, which serve multiple functions in maintaining telomere integrity. Complementary RNAs containing C-rich telomeric repeats, named ARIA, have also been identified in few yeast mutants and mammalian cells with dysfunctional telomeres. The molecular features and functions of ARIA remain understudied, mainly due to its low abundance and the […]
- by Chen, W., Maio, G., Chen, X., Lu, X., Zhao, J., Arora, N., Liu, Y., Ziolkowski, L. M., Macleod, K. F., Zhou, Y., Lin, H.KRAS mutations underlie many human cancers. While inhibitors such as Sotorasib and Adagrasib targeting KRAS mutants have shown promise, additional strategies are required to address the broader spectrum of KRAS-driven cancers, particularly those displaying drug resistance. Thus, there is a need to better understand KRAS signaling and develop new therapeutic strategies. Here we show that KRAS4A is palmitoylated on Cys180 by a palmitoyl transferase, DHHC7 (gene name ZDHHC7). Palmitoylation promotes KRAS4A plasma membrane localization, and more importantly, nanoclustering. This in […]
- by Sun, H., Kahnert, K., Hansen, J. N., Leineweber, W. D., Li, M., Feng, W., Ballllosera Navarro, F., Axelsson, U., Ouyang, W., Lundberg, E.The spatial organization of proteins within cells governs virtually all cellular functions. Yet, current imaging technologies can simultaneously visualize only tens of proteins, orders of magnitude below the thousands that populate a single human cell. Here, we present ProtiCelli, a deep generative model that simulates microscopy images for 12,800 human proteins from just three cellular landmark stains. Trained on 1.23 million images from the Human Protein Atlas, ProtiCelli outperforms existing methods in reconstruction accuracy and textural fidelity, and generalizes to […]
- by Li, L., Pohl, L., Hutloff, A., Niethammer, B., Thurley, K.Cytokine-mediated communication is a central mechanism by which immune cells coordinate activation, differentiation and proliferation. While mechanistic reaction-diffusion models provide detailed descriptions of cytokine secretion and uptake at the cellular scale, their computational cost limits their applicability to large and densely packed cell populations. Previously employed approximations of cytokine diffusion fields rely on assumptions that neglect the influence of cellular geometry and volume exclusion. In this work, we study a macroscopic description of cytokine diffusion and reaction dynamics based on […]